2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1
adenosine receptors
M. Lohse, K. Klotz, U. Schwabe, G. Cristalli, S. Vittori, and M. Grifantini. Naunyn Schmiedebergs Arch Pharmacol, 337 (6):
687-9(June 1988)Lohse, M J Klotz, K N Schwabe, U Cristalli, G Vittori, S Grifantini,
M In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1988
Jun;337(6):687-9..
Abstract
2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential
high affinity ligand for A1 adenosine receptors. Binding of 3HPIA
to A1 receptors of rat brain membranes was inhibited by CCPA with
a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent
compound N6-cyclopentyladenosine (CPA). Binding of 3HNECA to A2
receptors of rat striatal membranes was inhibited with a Ki-value
of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of
CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate
cyclase, a model for the A1 receptor, with an IC50-value of 33 nM,
and it stimulated the adenylate cyclase activity of human platelet
membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity
compares favourably with a 38-fold selectivity of CPA. Thus, CCPA
is an agonist at A1 adenosine receptors with a 4-fold higher selectivity
and 2-fold higher affinity than CPA, and a considerably higher selectivity
than the standard A1 receptor agonist R-N6-phenylisopropyladenosine
(R-PIA). CCPA represents the agonist with the highest selectivity
for A1 receptors reported so far.
Lohse, M J Klotz, K N Schwabe, U Cristalli, G Vittori, S Grifantini,
M In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1988
Jun;337(6):687-9.
%0 Journal Article
%1 Lohse1988c
%A Lohse, M. J.
%A Klotz, K. N.
%A Schwabe, U.
%A Cristalli, G.
%A Vittori, S.
%A Grifantini, M.
%D 1988
%J Naunyn Schmiedebergs Arch Pharmacol
%K & Adenosine/*analogs Adenylate Adipose Animals Blood Brain/drug Corpus Cyclase/metabolism Humans Platelets/drug Purinergic/drug Rats Striatum/drug Tissue/drug derivatives/pharmacology effects/*metabolism effects/enzymology/metabolism effects/metabolism Receptor
%N 6
%P 687-9
%T 2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1
adenosine receptors
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3216901
%V 337
%X 2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential
high affinity ligand for A1 adenosine receptors. Binding of 3HPIA
to A1 receptors of rat brain membranes was inhibited by CCPA with
a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent
compound N6-cyclopentyladenosine (CPA). Binding of 3HNECA to A2
receptors of rat striatal membranes was inhibited with a Ki-value
of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of
CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate
cyclase, a model for the A1 receptor, with an IC50-value of 33 nM,
and it stimulated the adenylate cyclase activity of human platelet
membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity
compares favourably with a 38-fold selectivity of CPA. Thus, CCPA
is an agonist at A1 adenosine receptors with a 4-fold higher selectivity
and 2-fold higher affinity than CPA, and a considerably higher selectivity
than the standard A1 receptor agonist R-N6-phenylisopropyladenosine
(R-PIA). CCPA represents the agonist with the highest selectivity
for A1 receptors reported so far.
@article{Lohse1988c,
abstract = {2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential
high affinity ligand for A1 adenosine receptors. Binding of [3H]PIA
to A1 receptors of rat brain membranes was inhibited by CCPA with
a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent
compound N6-cyclopentyladenosine (CPA). Binding of [3H]NECA to A2
receptors of rat striatal membranes was inhibited with a Ki-value
of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of
CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate
cyclase, a model for the A1 receptor, with an IC50-value of 33 nM,
and it stimulated the adenylate cyclase activity of human platelet
membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity
compares favourably with a 38-fold selectivity of CPA. Thus, CCPA
is an agonist at A1 adenosine receptors with a 4-fold higher selectivity
and 2-fold higher affinity than CPA, and a considerably higher selectivity
than the standard A1 receptor agonist R-N6-phenylisopropyladenosine
(R-PIA). CCPA represents the agonist with the highest selectivity
for A1 receptors reported so far.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Lohse, M. J. and Klotz, K. N. and Schwabe, U. and Cristalli, G. and Vittori, S. and Grifantini, M.},
biburl = {https://www.bibsonomy.org/bibtex/2271ef6afc3e0996b807f9ecea0a3dc10/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {834a5af86185b66e6c9c6ebe7214adfc},
intrahash = {271ef6afc3e0996b807f9ecea0a3dc10},
issn = {0028-1298 (Print) 0028-1298 (Linking)},
journal = {Naunyn Schmiedebergs Arch Pharmacol},
keywords = {& Adenosine/*analogs Adenylate Adipose Animals Blood Brain/drug Corpus Cyclase/metabolism Humans Platelets/drug Purinergic/drug Rats Striatum/drug Tissue/drug derivatives/pharmacology effects/*metabolism effects/enzymology/metabolism effects/metabolism Receptor},
month = Jun,
note = {Lohse, M J Klotz, K N Schwabe, U Cristalli, G Vittori, S Grifantini,
M In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's
archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1988
Jun;337(6):687-9.},
number = 6,
pages = {687-9},
shorttitle = {2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1
adenosine receptors},
timestamp = {2010-12-14T18:20:06.000+0100},
title = {2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1
adenosine receptors},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3216901},
volume = 337,
year = 1988
}